NMR-Screening

In both variants of the approach, i) and ii), the ligands detected in a NMR screen would be subjected to further modifications, and become larger during the design process. The properties of the compound library need to fulfill therefore a number of NMR-specific requirements. The compounds need to be soluble in water, their molecular properties should not exceed half the number that is defined in the Lipinski rules for molecular... 

Stockman BJ, Dalvit C (2002) NMR screening techniques in drug discovery and drug design. Prog NMR Spectrosc 41 187-231... 

Two distinct strategies are used in NMR screening. The first strategy looks for changes in the NMR spectrum of the protein target and the second looks for changes to the NMR spectrum of the ligand. 

An NMR screening strategy in which a small but diverse set of small molecules is screened against a potential drug target was recently described... 

Fig. 1.9 Analogues of JNK3 inhibitors identified using NMR screening.

Fig. 1.10 Cdk2 inhibitor identified using NMR screening by the WaterLOGSY method.

More than 2,000 potential replacements for the bromophenyl or pyridyl groups were then screened using the NMR-screening technique. Several fragments were identified which caused chemical shift changes in the desired binding site of the protein, amongst them indole (7) and 2-phenylimidazole... 

Recently, a number of NMR screening techniques based on the nuclear Overhauser effect (NOE) have been developed. 

Primary NMR Screening Using Spin Labels SLAPSTIC... 

In primary NMR screening, the following reasons make observation of the ligand resonances often preferable ... 

Validation and Preliminary Optimization of Primary NMR Screening Hits... 

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